This project is designed to study the basic mechanisms involved in the uterine uptake and retention of contraceptive progestins administered through "Uterine Progesterone System" so as to assess the overall bioavailability of contraceptive progestins in this particular route of administration. Various physiological factors such as the estrous cycle, uterine progestin receptors, and progestin binding macromolecules will also be studied to ascertain any effect these may have on the extent and rate of uterine absorption, retention, and distribution of contraceptive porgestins administered by the intraluminal route. The areas of research proposed in this project are:(1), the pharmacokinetics involved in the absorption, retention, and distribution of contraceptive progestins upon intrauterine administration; (2), the possible roles uterine progesterone receptors may play on the absorption, retention, disposition, and the overall action of contraceptive progestins administered by the intraluminal route; (3), the long-term effect of uterine tissues to various contraceptive progestins in vivo; and (4), the interplay between serum progestin-binding macromolecules and uterine progestin receptors on the overall distribution and pharmacodynamics of progestins in the uterus. BIBLIOGRAPHIC REFERENCES: "Uterine Retention of Progesterone Administered by Various Routes," Sen-Maw Fang, Ching-Shan Lin, and Vicky Lyon, Academy of Pharmaceutical Sci. (Abstract) 6, 138 (1976). "Uterine Retention of Progesterone Administered by Various Routes," Sen-Maw Fang, Ching-Shan Lin, and Vicky Lyon, Academy of Pharmaceutical Sci. (Abstract) 6, 139 (1976).